[Pharmacokinetic aspects of dosage increase of recombinant interferon alpha-2B in patients following intraperitoneal and intra-arterial application].
Interferon-alpha-2 b (IFN) was administered as an i.a. bolus at doses of 3 and 5 million international units (MIU), as an i.a. 24h long-time infusion at 3 and 5 MIU and as an i.p. 90 min short-time infusion at 5, 10 and 15 MIU. Dose escalation of IFN on i.p. administration leads to correspondingly elevated AUC values of IFN (correlating to the dose) in the peritoneal fluid (PF) and blood, with a shift of the steady-state at about 2h. Bioavailability of IFN is 30 times higher for PF than for blood. t1/2 el, Vd and total clearance are not influenced by dose escalation in both compartments due to their dose-independency. IFN is eliminated from the PF with t1/2 el = 10-32h and from the blood with t1/2 el = 5-13h. After an i.a. bolus at either dosage IFN is distributed from the blood with a half-life of below 2h. 24h infusion leads to a steady-state within 4-6h and a cmax of 8.5 or 12.5 units/ml, respectively. IFN is slowly eliminated during infusion with a t1/2 el of 16h.
Schüller
J
J
1. Medizinische Abteilung, Krankenanstalt Rudolfstiftung, Wien.
Wirth
M
M
Bosse
C
C
Fogl
U
U
Schernthaner
G
G
Czejka
M J
MJ
Micksche
M
M
D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007261:Infusions, Intra-Arterial; D007263:Infusions, Parenteral; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins
Pharmakokinetische Aspekte der Dosissteigerung von rekombinantem Interferon-alpha-2b in Patienten nach intraperitonealer (i.p.) und intraarterieller (i.a.) Applikation.